The type 1 insulin-like growth factor receptor (IGF-1R) is known to play an important role in aging. My laboratory has been interested for some time in the biology of the IGF-1R and its signaling. Recently, we have found that the IGF-1R, directly or indirectly, modulates the expression and/or the activity of three proteins, all of which have been implicated in aging, either in vivo or in vitro. These three proteins are: 1) the Id proteins, that are transcriptional factors involved in the control of cell proliferation and cell differentiation. The Idl protein has been shown to delay cellular senescence. 2) the Ras oncoprotein, which, in certain circumstances, induces a senescent-like state in cells in culture. 3) the p66 isoform of the Shc proteins, that plays a role in the longevity of mice. The involvement of the IGF-1R in the regulation of Id gene expression and the stabilization of Ras are findings original in our laboratory and completely novel. The role of p66 in IGF-IR signaling has been studied in other laboratories as well as ours, but very little information has emerged so far. The combination of a receptor and three signaling proteins all involved in aging constitute an area of investigation, that combines basic cell biology and relevance to aging. This project requires a close interaction with at least two other projects in the present application.